Association of small vessel ischemic white matter changes with BOLD fMRI imaging in the elderly

Abstract

White matter hyperintensities (WMHs) are often identified on T2-weighted magnetic resonance (MR) images in the elderly. The WMHs are generally associated with small vessel ischemic or pre-ischemic changes. However, the association of WMHs with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is understudied. In this study, we evaluate how the BOLD signal change is related to the presence of WMHs in the elderly. Data were acquired as part of a study of late-life depression and included elderly individuals with and without major depression. The subjects were pooled because the presence of depression was not significantly associated with task-related BOLD changes, task performance, and WMH distribution. A whole brain voxel-wise regression analysis revealed a significant negative correlation between WMH burden and BOLD signal change during finger-tapping in the parietal white matter. Our observation that WMHs are associated with a significant diminution of the BOLD signal change underscores the importance of considering cerebrovascular burden when interpreting fMRI studies in the elderly. The mechanism underlying the association of WMH and BOLD signal change remains unclear: the association may be mediated by changes in neural activation, changes in coupling between neuronal activity and hemodynamics, or, perhaps, secondary to the effect of the ischemic changes on the sensitivity of the T2* BOLD MR signal.

Abnormal White Matter Blood-Oxygen-Level–Dependent Signals in Chronic Mild Traumatic Brain Injury

“…In addition, these disorders do not produce BOLD signal abnormalities comparable to those reported here. 78,[94][95][96][97][98] Therefore, our results indicate that neither neuropsychological measures nor measures of predictive visual tracking eye movements accurately discriminated individual symptomatic chronic mTBI subjects from controls. These negative results were obtained concurrently with the promising accuracy of classification of chronic mTBI subjects observed using BOLD-fMRI measures in regions of the white matter.…”

“…76 In addition, these regions are close to a core of damaged tissue, including white matter tracts, basal ganglia, and upper brainstem, that has been found in severe TBI. 77 Interestingly, a recent paper 78 found that white matter hyper-intensity burden was associated with a BOLD signal decrease in white matter during a finger-tapping task. Therefore, our interpretation is that these regions show an abnormal BOLD signal due to a pathological process caused by the damage inflicted by TBI.…”

Brain Structural Connectivity in Late-Life Major Depressive Disorder

“…Multi-modal imaging research has confirmed that WMHs are associated with worse white matter microstructural integrity (55-57). Further, brain structural pathology is associated with altered brain function in LLD (64-66). This literature supports a conceptualization of LLD as a disconnection syndrome (Figure), wherein several physical health factors precede pathological changes to brain structural connectivity, which affects brain function, and leads to the clinical manifestations of LLD.…”

“…In LLD, prevalent WMHs are associated with altered functional MRI signal (64), including abnormal default-mode network connectivity (65) and more pronounced functional activation in response to an affective-reactivity task (66). White matter microstructural integrity (expressed as fractional anisotropy measured with DTI) also relates to resting state functional connectivity among older adults with depression (67).…”

A physiologic biomarker for cerebral amyloid angiopathy

“…CAA-related structural changes can affect every step involved in formation of the BOLD signal. 8 Namely, these structural lesions can change 1) neuronal activity and transmission of the signal generated by the stimulus; 2) coupling between neural activity and hemodynamic response, the latter representing a complex interaction between the structural integrity of the vessel's contractile components, cerebral blood flow, blood volume, and metabolic rate of oxygen consumption; and 3) the sensitivity of the regional T2* BOLD signal. The hope is to prove that a measure of BOLD signal would yield the best representation of the second point, namely the neurovascular coupling response.…”